Rheumatoid Arthritis
Conditions
Brief summary
The primary objective is to evaluate the safety and tolerability of TollB-001 following the administration of single or multiple oral doses in healthy adult subjects
Detailed description
This is a Phase I, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of single or multiple dose(s) of TollB-001 administered orally in healthy adult subjects and the food effect on the PK of a single dose of TollB-001 with a randomized, open-label and two-period crossover design. This study includes three parts. Part A: single ascending dose (SAD) study; Part B: multiple ascending dose (MAD) study; and Part C: FE study.
Interventions
DRUGTollB-001 tablets
TollB-001 treatment
DRUGTollB-001 placebo
TollB-001 Placebo
Sponsors
Toll Biotech Co. Ltd. (Beijing)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects between the age of 18 and 45 (both inclusive) when signing the informed consent form (ICF) 2. Able to give a signed written ICF (the consent form must be signed by the subject prior to any study-specific procedures); have a full understanding of the study content, procedures, and possible AEs; and be willing and able to comply with study procedures and follow-up examinations 3. Body mass index (BMI, weight \[kg\]/height2 \[m2\]) within 19.0-26.0 kg/m2 (both inclusive), with total body weight \> 50 kg for male subjects and \> 45 kg for female subjects. 4. The subjects must be willing to use efficient physical contraception methods with a contraceptive failure rate of\<1% with their reproductive age partners within 90 days from signing the ICF to the last administration of the investigational drug (such as condoms , intrauterine devices) 5. Male subjects must also be willing to refrain from donating sperm for 90 days from the first administration of the investigational drug to the last administration of the investigational drug 6. Results of vital signs, physical examination, laboratory examinations, abdominal and urinary B-ultrasound, 12-lead ECG, and other examination are normal or abnormal but not clinically significant. QT interval corrected for heart rate according to Fridericia's formula (QTcF) must be within the following ranges: QTcF ≤ 450 msec for male subjects, and QTcF ≤ 470 msec for female subjects. Assessment may be repeated if deemed appropriate by the investigator. 7. Ability to swallow all IMPs.
Exclusion criteria
Subjects were excluded if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Red blood cell count(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | Red blood cell count |
| hematocrit(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | hematocrit |
| hemoglobin(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | hemoglobin |
| white blood cell count(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | white blood cell count |
| whiteblood cell differential count(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | whiteblood cell differential count |
| plateletcount(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | plateletcount |
| Alanine aminotransferase(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | Alanine aminotransferase |
| aspartateaminotransferase(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | aspartateaminotransferase |
| alkaline phosphatase(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | alkaline phosphatase |
| gamma-glutamyl transpeptidase(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | gamma-glutamyl transpeptidase |
| total bilirubin(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | total bilirubin |
| direct bilirubin(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | direct bilirubin |
| blood ureanitrogen (or blood urea)(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | blood ureanitrogen (or blood urea) |
| creatinine(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | creatinine |
| glucose(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | glucose |
| total protein(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | total protein |
| creatine kinase(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | creatine kinase |
| Activated partial thromboplastin time(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | Activated partial thromboplastin time |
| prothrombin time(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | prothrombin time |
| internationalnormalized ratio(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | internationalnormalized ratio |
| fibrinogen(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | fibrinogen |
| urine pH(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine pH |
| urine specific gravity(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine specific gravity |
| urine glucose(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine glucose |
| urine protein(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine protein |
| urobilinogen(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urobilinogen |
| urine bilirubin(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine bilirubin |
| urine leukocyte(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine leukocyte |
| urine ketone body(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine ketone body |
| urine red blood cells(physiological parameter) by investigator | Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days) | urine red blood cells |
| AE/SAE monitoring by ToxicityGrading Scale for Healthy Adults and Volunteers Enrolled in Preventative Vaccine Trials,2007 (70 FR 22664) | First dose up to last follow-up visit（for a maximum of 20 days） | AE/SAE monitoring |
| physical examination(physiological parameter) by investigator | First dose up to last follow-up visit（for a maximum of 20 days）;SAD:Screening,Day2,Day5 or ET Visit;MAD:Screening,Day3,Day6,Day9 or ET Visit;FE:Screening,Period 1 Day2,Period 1 Day5;Period 2 Day-1,Period 2 Day2,Period 2 Day5 or ET Visit. | The assessments of general appearance, head(including ears, eyes, nose, throat), neck, skin, cardiovascular system, respiratory system,abdominal system, nervous system, musculoskeletal system, and lymphatic system |
| blood pressure(systolic pressure and diastolic pressure)(physiological parameter) by investigator | For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 to Day9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit. | blood pressure(systolic pressure and diastolic pressure) |
| pulse(physiological parameter) by investigator | For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit. | pulse |
| respiratory rate(physiological parameter) by investigator | For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit. | respiratory rate |
| body temperature(physiological parameter) by investigator | For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit. | body temperature |
| 12-lead ECGs | For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 to Day9 or ET Visit;FE:Screening,Period 1 Day1,Period 1 Day3,Period 1 Day5;Period 2 Day-1,Period 2 Day1,Period 2 Day3,Period 2 Day5 or ET Visit. | ECGs done in triplicate; heart rate, PR interval, QT and QTc interval and QRS duration |
| B-ultrasound(physiological parameter) by investigator | For a maximum of 20 days;SAD:Screening,Day5 or ET Visit;MAD:Screening,Day9 or ET Visit;FE:Screening,Period 1 Day5;Period 2 Day5 or ET Visit. | liver, gallbladder, spleen, pancreas, kidney and bladder |
Countries
China
Contacts
Primary Contactmin xv, Master
Backup Contactxuehong deng, Doctor
Outcome results
None listed